A critical aspect of the Program Project application includes the in vivo analysis of DC function in specifically genetically engineered strains of mice. Two general types of mouse strains will be routinely utilized-those severely immunocompromised via the result of specific gene deletions in immune functions and autoimmune strains of mice that are hyper-responsive to a variety of antigen stimuli. The goals of the Program Project application involve the manipulation of these animals to determine the role of innate DCs in maintaining tolerance and the pathways that are involved in that vital function. The generation and maintenance of these strains will be the function of the Animal Services Core headed by Dr. Tarakhovsky. The purpose of this Core will be to provide segregated facilities for the housing and breeding of the animal strains proposed in this Program Project. To support that function, the Director of Laboratory Animal Research Center (LARC), Mr. Fred Quimby, has agreed to work with the Program Project investigators to implement the level of animal husbandry necessary. A full-time animal technician dedicated to this purpose will be required to provide the additional care these animals require, including: bi-weekly bedding changes; prophylactic antibiotic treatment; and the sterilization of all cages, bedding, and food. This cost, along with the per diem established by the LARC for standard animal care, will cover the additional services required.